Project Summary/Abstract: It is well known that individuals with Down syndrome (DS) suffer from significant ocular complications including high levels of lower-order refractive error (sphere and cylinder) and elevated levels of higher-order aberrations. These optical factors likely contribute to the poor acuity observed in this population and are a substantial target of our long-term goal to provide new treatment strategies to improve vision in this group. Current clinical prescribing practices under-serve this community, as the cognitive demands of the subjective refraction sequence are difficult for this population and often leave clinicians to prescribe from objective clinical findings that target full correction of sphero-cylindrical refractive error. This prescribing practice can lead to sub-par outcomes given the fact that full lower-order corrections can exacerbate the effects of higher-order aberrations in more aberrated eyes. The short-term goal of this work is to optimize spectacle corrections for patients with DS by considering the unique aberration structure of each eye and then evaluate the performance of these corrections in a treatment trial. The central hypothesis is that measures of retinal image quality (metrics) can be used to identify alternative lower-order corrections that balance the effects of lower and higher-order aberrations to optimize vision. This hypothesis is substantiated by preliminary data demonstrating multi-line improvements in visual acuity of observers reading charts that simulate the optics of DS eyes with these optimized corrections. This objective prescribing strategy will be further substantiated in this work by three specific aims: 1) Identify metrics that, when maximized, consistently provide improvements over full lower-order corrections for DS eyes, as judged by control observers. 2) Test the ability of metric-derived corrections from Aim 1 to outperform clinically derived corrections in patients with DS in a randomized treatment trial. 3) Evaluate whether subjects in Aim 2 fully benefitted from metric-derived corrections by comparing measured acuity gains from subjects with DS to predicted acuity gains from controls viewing charts simulating the optics for subjects with DS for each correction. This approach is innovative in that it removes the barrier of subjective input to the refraction process and allows the clinician to consider lower- order corrections that target overall image quality, rather than simply mitigating the effects of lower-order refractive error. This proposed research is significant in that it proposes to use the most accessible treatment strategy for this population of patients (spectacles) in an optimized manner to remove a significant barrier for individuals with DS. Multi-line improvements in acuity are anticipated to increase access to traditional print sizes, facilitate vocational efforts, and assist in activities of daily living, all of which may promote greater independence. The application of this work is far-reaching to other patients who cannot fully participate in subjective refractions (young children, cognitively impaired, etc.) and those with elevated levels of aberrations who require improved spectacle performance (corneal disease, poor surgical outcomes, etc.).